ABSTRACT This Core provides a range of biophysical, spectroscopy, and imaging technologies for characterizing HIV components, host cell factors, and their interactions in solution, cells, and animals. These capabilities allow us to study HIV and host components at all scales of resolution, from atomic-resolution structural analyses to whole-organism pathogenesis in vivo. As we have previously done, we will use a suite of biophysical approaches to characterize the biophysical properties and interaction energetics of HIV and host macromolecules.1-10 Structures and conformations of host proteins and HIV proteins and RNA are also investigated using NMR spectroscopy.7,8,10-22 Fluorescence imaging is used in single-molecule studies of the composition, conformation, and activities of viral and cellular machines23-26, and is also used to track and visualize the dynamics of single-cell infection events.27-29 Finally, HIV pathogenesis will be studied at the resolution of whole-animal infections using a variety of in vivo imaging techniques (non-invasive bioluminescence, fluorescence, and PET imaging) at the tissue and cellular level (intravital imaging and light microscopy of clarified samples) and at molecular resolution (tissue electron tomography).30-36